Combination of either of the two ALK inhibitors with Nutlin-3 strongly induced the efflux of cytochrome c and activation of Caspase-9, which is known to be another marker of the intrinsic apoptosis pathway (Fig 5a,c); In contrast, activation of Caspase 8, which is known to be a marker of the extrinsic apoptosis pathway, was not detected in the ALK-amplified NB cell lines. This evidence concerns the gene CASP8 and neuroblastoma.